Graus F, Dalmou J, Reñé R, Tora M, Malats N, Verschuuren J J, Cardenal F, Viñolas N, Garcia del Muro J, Vadell C, Mason W P, Rosell R, Posner J B, Real F X
Service of Neurology, Hospital Clínic i Provincial, Barcelona, Spain.
J Clin Oncol. 1997 Aug;15(8):2866-72. doi: 10.1200/JCO.1997.15.8.2866.
Anti-Hu antibodies (HuAb) recognize antigens expressed by neurons and small-cell lung cancer (SCLC). High titers of HuAb were initially reported in serum from patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) and SCLC. Preliminary studies have indicated that some SCLC patients without PEM/SN harbor low titer of HuAb in their serum, and that the SCLC of these patients may grow more indolently. Based on these observations, we conducted a multicenter prospective study of SCLC patients without PEM/SN to determine the incidence and prognostic implications of HuAb.
Serum samples were collected at diagnosis of SCLC in 196 patients without PEM/SN. HuAb were determined by immunoblot of purified recombinant HuD antigen.
HuAb were detected in 32 (16%) of the 196 patients. Of the 170 patients who received treatment for the tumor, 27 (16%) were HuAb positive. HuAb was associated with limited disease stage (59.3% v 38.6%; P = .047), complete response to therapy (55.6% v 19.6%; P < .001), and longer survival (14.9 v 10.2 months; P = .018). In a logistic regression analysis, HuAb status was an independent predictor of complete response induction. The probability of achieving a complete response was more than five times higher in HuAb-positive than in HuAb-negative patients (odds ratio, 5.4; 95% confidence interval, 1.71 to 16.89; P = .004). Cox multivariate analysis indicated that HuAb status was not independently associated with survival.
The presence of HuAb at diagnosis of SCLC is a strong and independent predictor of complete response to treatment. This feature accounts for the association between HuAb and longer survival.
抗Hu抗体（HuAb）可识别神经元和小细胞肺癌（SCLC）表达的抗原。最初报道在副肿瘤性脑脊髓炎/感觉神经病（PEM/SN）患者及SCLC患者的血清中存在高滴度的HuAb。初步研究表明，一些无PEM/SN的SCLC患者血清中存在低滴度的HuAb，且这些患者的SCLC生长可能较为惰性。基于这些观察结果，我们对无PEM/SN的SCLC患者进行了一项多中心前瞻性研究，以确定HuAb的发生率及其对预后的影响。
收集196例无PEM/SN的SCLC患者诊断时的血清样本。通过纯化重组HuD抗原的免疫印迹法检测HuAb。
196例患者中有32例（16%）检测到HuAb。在170例接受肿瘤治疗的患者中，27例（16%）HuAb呈阳性。HuAb与疾病分期局限（59.3%对38.6%；P = 0.047）、对治疗的完全缓解（55.6%对19.6%；P < 0.001）及更长的生存期（14.9个月对10.2个月；P = 0.018）相关。在逻辑回归分析中，HuAb状态是诱导完全缓解的独立预测因素。HuAb阳性患者实现完全缓解的概率比HuAb阴性患者高五倍多（优势比，5.4；95%置信区间，1.71至16.89；P = 0.004）。Cox多变量分析表明，HuAb状态与生存期无独立相关性。
SCLC诊断时HuAb的存在是对治疗完全缓解的有力且独立的预测因素。这一特征解释了HuAb与更长生存期之间的关联。
